Global Warming Potential* (GWP*): Understanding the implications for mitigating methane emissions in agriculture

KEY MESSAGES: - GWP* (global warming potential) complements conventional climate metrics such as GWP100 because GWP* better describes the actual warming caused by methane (CH4) emissions. For example, using GWP100, a constant annual rate of CH4 emissions may be misinterpreted as having a 3-4 times higher impact on warming than observed. The use of GWP* can correct this misestimation. - GWP* was used here to evaluate the impact of agricultural CH4 emissions scenarios from 2020- 2040, finding that: - A sustained ~0.35% annual decline is sufficient to stop further increases in global temperatures due to agricultural CH4 emissions. This is analogous to the impact of net-zero CO2 emissions. - A ~5% annual decline could neutralize the additional warming caused by agricultural CH4 since the 1980s. - Faster reductions of CH4 emissions have an analogous impact to removing CO2 from the atmosphere. - However, a 1.5% annual increase in CH4 emissions would lead to climate impacts about 40% greater than indicated by GWP100. - The application of GWP* to CH4 emissions accounting suggests that avoiding further warming due to CH4 emissions in agriculture is more attainable than previously understood. CH4 reductions can have a rapid and highly substantial impact, which underscores the importance of making significant cuts in CH4 emissions immediately

Vitamin E reverses multidrug resistance in vitro and in vivo

Multidrug resistance (MDR) is a major obstacle to successful and effective chemotherapeutic treatments of cancers. This study explored the reversal effects of vitamin E on MDR tumor cells in vitro and in vivo, elucidating the potential mechanism of this reversal. VE at a concentration of 50 μM exhibited a significant reversal of the MDR effect (compared to only PTX in DMSO, p < 0.05) in two human MDR cell lines (H460/taxR and KB-8-5). The MDR cell xenograft model was established to investigate the effect of VE on reversing MDR in vivo. Mice intravenously injected with Taxol (10 mg/kg) with VE (500 mg/kg, IP) showed an ability to overcome the MDR. VE and its derivatives can significantly increase intracellular accumulation of rhodamine 123 and doxorubicin (P-gp substrate), but not alter the levels of P-gp expression. These treatments also did not decrease the levels of intracellular ATP, but were still able to inhibit the verapamil-induced ATPase activity of P-gp. The new application of VE as an MDR sensitizer will be attractive due to the safety of this treatment

Key Structure of Brij for Overcoming Multidrug Resistance in Cancer

Multidrug resistance (MDR) is a major barrier to the chemotherapy treatment of many cancers. However, some non-ionic surfactants, for example Brij, have been shown to restore the sensitivity of MDR cells to such drugs. The aim of this study was to explore the reversal effect of Brij on MDR tumor cells and elucidate its potential mechanism. Our data indicate that the structure of Brij surfactants plays an important role in overcoming MDR in cancer, i.e. modified hydrophilic-lipophilic balance (MHLB, the ratio of the number (n) of hydrophilic repeating units of ethylene oxide (EO) to the number (m) of carbons in the hydrophobic tail (CH2).). Cell viability of cells treated with paclitaxel (PTX) nanocrystals (NCs) formulated with Brij showed positive correlations with MHLB (R2 = 0.8195); the higher the ratio of Brij to PTX in NCs, the higher cytotoxicity induced by the PTX NCs. Significant increases in intracellular accumulation of 3H-PTX (P-gp substrate) were observed in an MDR cell line (H460/taxR cells) treated with Brij 78 (MHLB=1.11) and Brij 97 (MHLB=0.6). After treatments with Brij 78 and Brij 97, the levels of intracellular ATP were decreased and verapamil induced ATPase activities of P-gp were inhibited in multidrug resistant cells. The responses of the cells to Brij 78 and Brij 97 in ATP depletion studies correlated with the cell viability induced by PTX/Brij NCs and intracellular accumulation of 3H-PTX. Brij 78 and Brij 97 could not alter the levels of P-gp expression detected by western blotting. These findings may provide some insight into the likelihood of further development of more potent P-gp inhibitors for the treatment of MDR in cancer

Multifunctional Nanoparticles Based on a Single-Molecule Modification for the Treatment of Drug-Resistant Cancer

Multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. Tocopheryl polyethylene glycol 1000 succinate (TPGS) has been extensively explored for the treatment of MDR in cancer because of its ability to inhibit P-glycoprotein. Here, we have established multifunctional nanoparticles (MFNPs) using a single-molecule modification of TPGS, which can deliver a hydrophobic drug, paclitaxel (PTX), and a hydrophilic drug, fluorouracil (5-FU), and overcome MDR in cancer. Our data indicated that, when delivered into a PTX-resistant cell line using MFNPs, the combination of PTX and 5-FU was more cytotoxic than each agent individually

Shape-Controlled Paclitaxel Nanoparticles with Multiple Morphologies: Rod-Shaped, Worm-Like, Spherical, and Fingerprint-Like

Although many nanocarriers have been developed to encapsulate paclitaxel (PTX), the drug loading and circulation time in vivo always are not ideal because of its rigid “brickdust” molecular structure. People usually concentrate their attention on the spherical nanocarriers, here paclitaxel nanoparticles with different geometries were established through the chemical modification of PTX, nanoprecipitation, and core-matched cargos. Previously we have developed rod-shape paclitaxel nanocrystals using block copolymer, pluronic F127. Unfortunately, the pharmacokinetic (PK) profile of PTX nanocrystals is very poor. However, when PTX was replaced by its prodrug, the geometry of the nanoparticles changed from rod-shaped to worm-like. The worm-like nanoparticles can be further changed to spherical nanoparticles using the nanoprecipitation method, and changed to fingerprint-like nanoparticles upon the addition of the core-matched PTX. The nanoparticles with nonspherical morphologies, including worm-like nanoparticles and fingerprint-like nanoparticles, offer significant advantages in regards to key PK parameters in vivo. More important, in this report the application of the core-matching technology in creating a core-matched environment capable of controlling the in vivo PK of paclitaxel was demonstrated, and it revealed a novel technique platform to construct nanoparticles and improve the poor PK profiles of the drugs

Multifunctional Nanoparticles Based on a Single-Molecule Modification for the Treatment of Drug-Resistant Cancer

Multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. Tocopheryl polyethylene glycol 1000 succinate (TPGS) has been extensively explored for the treatment of MDR in cancer because of its ability to inhibit P-glycoprotein. Here, we have established multifunctional nanoparticles (MFNPs) using a single-molecule modification of TPGS, which can deliver a hydrophobic drug, paclitaxel (PTX), and a hydrophilic drug, fluorouracil (5-FU), and overcome MDR in cancer. Our data indicated that, when delivered into a PTX-resistant cell line using MFNPs, the combination of PTX and 5-FU was more cytotoxic than each agent individually